Multicenter Osteoarthritis Study (MOST) Renewal

描述(申请人提供)：骨关节炎(OA)是最常见的关节炎形式，仍然是为数不多的慢性衰老疾病之一，几乎没有有效的治疗方法和预防策略。有症状的膝骨性关节炎影响了12%的老年人，尽管医学上取得了进步，但对许多受影响的人来说，膝骨性关节炎仍然是疼痛和功能限制的主要来源。MOST研究是第一次大规模观察性研究，重点关注膝骨性关节炎患者或高危人群。MOST的中心目标是确定可更改的风险因素。为了实现这一目标，我们招募了3026名膝关节骨关节炎患者，并对他们进行了跟踪调查，这些患者要么在基线水平患有膝骨性关节炎，要么因为有一个或多个疾病危险因素而处于疾病高危状态。我们建议对MOST进行续签。为了继续跟踪这一独特的队列，我们将解决代表三个研究主题的一系列新问题：机械风险因素、膝关节症状的原因和长期疾病轨迹。对影响膝关节负荷的危险因素的关注反映了大多数研究人员的观点，即骨关节炎是一种机械驱动的疾病。机械风险因素很可能既与疾病风险密切相关，又是可改变的。疼痛是骨性关节炎的主要症状，也是影响其临床和公共卫生的主要原因。对疼痛敏感性的研究试图更好地了解维持或放大骨性关节炎症状的神经机制。与膝骨性关节炎相关的另一个症状是膝屈曲，其频率和影响最近才被描述，其与老年人跌倒和骨折的关系尚不清楚。最后，我们将利用两个关于功能丧失的综合信息和重复的磁共振成像的赠款周期来解决这种慢性疾病的长期轨迹。在MOST研究的更新中，我们将重新检查一组已经患有疾病或有高风险感染的人，以评估疾病的危险因素。然后，可以针对那些被证明与疾病发展或进展有关的因素进行风险因素修改，从而为疾病预防提供独特的机会。要研究的风险因素包括许多实际可以修改的因素，包括力量、走路方式和平衡。此外，MOST将提供迄今为止关于膝关节结构变化与其对疼痛和功能的影响之间关系的最好理解，为治疗提供结构性靶点。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and remains one of the few chronic diseases of aging for which there is little if any effective treatment and few preventive strategies. Symptomatic knee osteoarthritis affects 12% of elders and despite medical advances, remains, for many affected, a major source of pain and function limitation. The MOST study is the first large scale observational study to focus on persons with or at high risk of knee osteoarthritis. The central goal of MOST is to identify modifiable risk factors. To accomplish this, we recruited and have followed 3026 persons who either had knee osteoarthritis at baseline or were at high risk of developing disease because they had one or more disease risk factors. We are proposing a renewal of MOST. In continuing to follow this unique cohort, we will address a series of new questions representing three investigative themes: mechanical risk factors, causes of knee symptoms and long term disease trajectory. The focus on risk factors which affect knees on the basis of loading reflects the view of MOST investigators that OA is a mechanically driven disease. Mechanical risk factors are likely to be both strongly associated with disease risk and modifiable. Pain is the cardinal symptom of OA and the main cause of its clinical and public health impact. An investigation of pain sensitivity seeks to better understand the neurological mechanisms that sustain or magnify OA symptoms. Another symptom associated with knee OA is knee buckling, whose frequency and impact has only recently been described and whose association with falls and fractures in older adults is unknown. Lastly, we will take advantage of two grant cycles of comprehensive information on functional loss and repeated MRI's to address the long term trajectory of this chronic disease. In this renewal of the MOST study we will re-examine a group of persons who already have disease or are at high risk of getting it, to evaluate the risk factors for disease. Those factors that prove to be related to disease development or progression could then be targeted for risk factor modification offering unique opportunities for disease prevention. Risk factors to be studied include many which are practical to modify, including strength, ways of walking, and balance. Also, MOST will provide the best understanding yet of the relation between changes in knee structures and their effects on pain and function, providing structural targets for treatment.